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2005 Grant - Lamb

Gene-Environment Interactions in Alzheimer's Disease Mouse Models

Bruce Lamb, Ph.D.Case Western Reserve UniversityCleveland, Ohio

2005 Zenith Fellows Award

Most researchers agree that late-onset Alzheimer's disease is caused by a complex set of genetic and environmental factors, such as diet, blood pressure, education, social interaction, and others. Clarifying how these various factors interact and influence one another is a significant challenge.

Bruce Lamb, Ph.D., and colleagues have developed four strains of mice that carry human Alzheimer-related genes. The genome of each strain has been sequenced, or in other words, they have a detailed "script" of the entire genetic code for each strain. In subsequent assessments of the Alzheimer-like disease in each line of mice, the researchers may be able to correlate genetic variations, environmental factors and variability in pathology.

In this current study, the investigators are examining the interactions of genetic factors and high-fat, high-cholesterol diets. Preliminary research demonstrated that although all four strains experienced comparable increases in weight, only one strain exhibited changes in pathology. In further experiments, they aim to characterize the genetic factors that may account for these pathological variations. They will also assess the impact of cholesterol-lowering treatments among mice with different genetic backgrounds. This work may establish a foundation for examining the complex interactions of genetics, environmental factors and therapeutic strategies.